Evidence map›Paper›PMID 39394482›Full record

ArticleNature biotechnology2025

Model-directed generation of artificial CRISPR-Cas13a guide RNA sequences improves nucleic acid detection.

Sreekar Mantena, Priya P Pillai, Brittany A Petros, Nicole L Welch, Cameron Myhrvold, Pardis C Sabeti, Hayden C Metsky

Abstract read
In one paragraph

Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed.

  1. Article
  2. Rapid Cas13a-basedmSphere · 2026
    Article
  3. Machine Learning for CRISPR-Based Diagnostics.International journal of molecular sciences · 2026
    Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Facilitating crRNA Design by Integrating DNA Interaction Features of CRISPR-Cas12a System.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  15. Article
  16. Article
  17. Towards AI-designed genomes using a variational autoencoder.Proceedings. Biological sciences · 2024
    Article
  18. Article
  19. RNA structure modulates Cas13 activity and enables mismatch detection.bioRxiv : the preprint server for biology · 2023
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Sreekar MantenaBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-8834-1461
Priya P PillaiBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Brittany A PetrosBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2110-7475
Nicole L WelchBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Cameron MyhrvoldDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0000-0002-8971-184X
Pardis C Sabeti *Broad Institute of MIT and Harvard, Cambridge, MA, USA. pardis@broadinstitute.org.ORCID http://orcid.org/0000-0002-9843-1890
Hayden C Metsky *Broad Institute of MIT and Harvard, Cambridge, MA, USA. hayden@broadinstitute.org.ORCID http://orcid.org/0000-0002-8871-2349

Funding

Viral Genomics: evolution, spread, and host interactionsU19AI110818 · NIAID · BROAD INSTITUTE, INC. · PI BIRREN, BRUCE W., NEAFSEY, DANIEL E · 2014 to 2024
$66.5M
Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Medical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7M
West African Emerging Infectious Disease Research Center (WA-EIDRC)U01AI151812 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI ANDERSEN, KRISTIAN GRAUGAARD, GARRY, ROBERT F · 2020 to 2024
$13.2M
Computational Methods for Designing Optimal Genomics-guided Viral DiagnosticsK01AI163498 · NIAID · BROAD INSTITUTE, INC. · PI METSKY, HAYDEN C · 2021 to 2022
$232k
Bill & Melinda Gates Foundation INV-034761Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID) U01AI151812Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID) U19AI110818Gates Foundation INV-034761NCEZID CDC HHS NU50CK000629NIAID NIH HHS K01 AI163498NIAID NIH HHS U01 AI151812NIAID NIH HHS U19 AI110818NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM144273United States Department of Defense | Defense Advanced Research Projects Agency (DARPA) D18AC00006U.S. Department of Health & Human Services | Centers for Disease Control and Prevention (CDC) 75D30122C15113U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) K01AI163498U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) T32GM007753U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) T32GM144273
6 · The paper itself

Abstract

CRISPR guide RNA sequences deriving exactly from natural sequences may not perform optimally in every application. Here we implement and evaluate algorithms for designing maximally fit, artificial CRISPR-Cas13a guides with multiple mismatches to natural sequences that are tailored for diagnostic applications. These guides offer more sensitive detection of diverse pathogens and discrimination of pathogen variants compared with guides derived directly from natural sequences and illuminate design principles that broaden Cas13a targeting.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsRNA, Guide, CRISPR-Cas SystemsAlgorithmsBase SequenceRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID39394482
PMCPMC12439118

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.